Abstract:

INTRODUCTION
Tuberculosis remains a major public health threat globally and the Human
Immunodeficiency Virus (HIV) pandemic afflicting developing and developed
countries has resulted in enormous increases in tuberculosis infections
worldwide. Researchers have previously documented very low plasma vitamin C
levels in patients with active pulmonary tuberculosis. This was attributed to a
number of factors including: accelerated turnover of vitamin C, shifts in plasma
concentrations, increased collagen formation and tissue repair and decreased
vitamin C intake. Vitamin C appears to have a role in steroid-genesis and
catecholamine synthesis. Decreased plasma vitamin C levels may therefore
impact on the stress hormone response and acute phase reaction of patients
with active tuberculosis.
AIM
The primary aims of the study were to measure plasma vitamin C levels, as well
as stress hormone levels and acute phase reaction in patients with newly
diagnosed active pulmonary tuberculosis and control patients (without tuberculosis), to determine if there was any relationship between vitamin C
levels and the levels of these other variables.
METHODS AND MATERIALS
This was a prospective study of seventy one (71) consecutive patients admitted
to Helen Joseph Hospital (between March and October 2002) with newly
diagnosed active pulmonary tuberculosis and eighty nine (89) control patients
with medical conditions other than tuberculosis. Demographic, clinical and
laboratory data were captured and analyzed using SPSS 7.5 soft-ware.
Continuous variables were analyzed using students t-test. Categorical data were
analyzed by non parametric analysis and Pearsons linear regression model was
used to determine the correlation between vitamin C and the other variables in
the two groups.
RESULTS
There were no differences in race, gender, age, suburb of residence and
occupational distributions in the study group with tuberculosis compared to the
control group. There were more smokers and consumers of alcohol in the
control group (54 and 62 patients respectively) than in the study group (28 and
31 patients respectively). The study patients had lower blood pressure (average
90/40 mmHg versus 100/60 mmHg of controls), higher mean pulse rate (101.87 ±
15.14 beats/minute versus 82.92 ± 8.88 beats/minute, p< 0.01), higher mean
temperature (38.66 ± 0.67oC versus 37.14 ± 0.44oC, p< 0.01), and lower body
mass index (18.29 ± 3.80 Kg/ M2 versus 23.20 ± 5.35 Kg/ M2, p< 0.01).
Laboratory data comparing study group and controls also showed marked
differences as follows: White cell count (WCC) 8.68×106 / L ± 5.44 versus
11.00×106 / L ± 4.94, p = 0.01; Haemoglobin 9.56gm / dl ± 1.93 versus 12.92gm /
dl ± 2.34, p < 0.01 and platelet count 369.21× 106/L ± 190.71 versus 295.94×106
/ L ± 94.64, p = 0.01. White cell vitamin C levels (normal range – 20-40 μg/108
leucocytes) were low in half of the patients in both groups (study patients mean
29.85 ± 28.70μg/108 leucocytes versus controls 31.39 ± 30.24μg/108 leucocytes,
p = NS). Plasma vitamin C levels were reduced (normal range 10-20 mg/ml) in
both groups but more so in the controls (mean 3.87 ± 2.82 mg/ml versus 4.81 ±
3.21 mg / ml in study patients, p= 0.053). Mean cortisol levels were slightly
higher in the study patients (448.11 ± 197.41ηmol/L) than controls (392.70 ±
191.25ηmol/L, p = NS). Norepinephrine levels were slightly higher in the study
patients than controls (study patients mean 2531.61 ± 2043.60 ρmol/L versus
2178.98 ± 1719.98 ρmol/L of controls, p = NS). Dopamine levels were higher in
the study patients than in the controls (468.42 ± 377.57 ρmol/L in study patients
versus 293.37 ± 355.84 ρmol/L in controls, p = 0.01). Epinephrine levels were
higher in the controls (control patients mean 680.64 ± 743.78 ρmol/L versus
449.41 ± 380.04 ρmol/L of the study patients, p = 0.03). Ferritin levels were much
higher in the study patients compared with controls (study patients mean 3005.87
± 5023.26 μg/L versus 466.51 ± 1774.76 μg/L of the controls, p<0.01) as were CRP levels (125.91 ± 54.77 mg/L in the study patients versus 77.22 ± 81.17
mg/L in the controls, p=0.01). Mean urine cotinine levels were 16.42 ± 24.26μM/L
for controls and 9.28 ± 11.59 μM / L for the study patients (p=0.027). Correlation
studies did not show any significant differences between the different variables.
There was an inverse correlation between CRP levels and urine cotinine levels in
the control group (R squared=0.058 and p= 0.024).
DISCUSSION
There were no differences in the demographic profile of the two groups. Smoking
and alcohol consumption were more common in the control group than in the
study patients. Over 90 % of patients in both groups had low plasma vitamin C
levels, while half of the patients in each group had low white cell vitamin C levels.
The low levels of vitamin C could be due to some of the reasons given above or
possibly due to the fact that generally there are low levels in Africans for reasons
that are not apparent. The control group had increased mean urine cotinine
levels suggesting a possible influence of cigarette smoking on vitamin C
homeostasis in these patients. In both groups, the majority of patients had
normal cortisol levels as well as normal to high catecholamine levels. Also,
Ferritin and CRP levels were much higher in the study group than in the controls.
The low levels of vitamin C did not, however, have any relationship with stress
hormone levels and acute phase reactants.
CONCLUSION
This study has reaffirmed low plasma and white cell vitamin C levels in patients
with new onset pulmonary tuberculosis but has also found low levels in control
patients with diseases other than pulmonary tuberculosis. The study
demonstrates adequate stress hormone responses in tuberculosis patients,
which was not different from non- tuberculosis patients. Acute phase responses
were found to be of higher magnitude in tuberculosis patients than in the
controls. There were, however, no correlations between plasma vitamin C and
stress hormones or acute phase reactants.